The effect of caffeic acid phenethyl ester on the functions of human monocyte-derived dendritic cells.

BACKGROUND: Propolis, an ancient herbal medicine, has been reported the beneficial effect both in asthma patients and murine model of asthma, but the mechanism was not clearly understood. In this study, the effect of caffeic acid phenethyl ester (CAPE), the most extensively studied components in propolis, on the functions of human monocyte-derived dendritic cells (MoDCs) was investigated. RESULTS: CAPE significantly inhibited IL-12 p40, IL-12 p70, IL-10 protein expression in mature healthy human MoDCs stimulated by lipopolysaccharides (LPS) and IL-12 p40, IL-10, IP-10 stimulated by crude mite extract. CAPE significantly inhibited IL-10 and IP-10 but not IL-12 expression in allergic patients' MoDCs stimulated by crude mite extract. In contrast, the upregulation of costimulatory molecules in mature MoDCs was not suppressed by CAPE. Further, the antigen presenting ability of DCs was not inhibited by CAPE. CAPE inhibited IkappaBalpha phosphorylation and NF-kappaB activation but not mitogen-activated protein kinase (MAPK) family phosphorylation in human MoDCs. CONCLUSION: These results indicated that CAPE inhibited cytokine and chemokine production by MoDCs which might be related to the NF-kappaB signaling pathway. This study provided a new insight into the mechanism of CAPE in immune response and the rationale for propolis in the treatment of asthma and other allergic disorders.

Armillariella mellea induces maturation of human dendritic cells without induction of cytokine expression.

ETHNOPHARMACOLOGICAL RELEVANCE: Armillariella mellea, an edible and medicinal mushroom possessing immuno-modulating potential, has been frequently used for the treatment of infectious diseases or cancers. AIM OF THE STUDY: In order to elucidate immune-regulatory mechanisms of Armillariella mellea, we investigated the effect of water-soluble components from Armillariella mellea (AME) on the regulation of human dendritic cell (DC) maturation and activation. MATERIALS AND METHODS: Immature DCs (iDCs) were prepared by differentiating human peripheral blood CD14-positive cells with GM-CSF and IL-4. Then, iDCs were treated with AME at 2-20 microg/ml for 48 h and subjected to flow cytometry to analyze the expression of DC markers. Dextran-FITC uptake assay and enzyme-linked immunosorbent assay were performed to examine the endocytic capacity of AME-stimulated DC and their production of cytokines, respectively. RESULTS: iDCs stimulated with AME showed representative features during DC maturation such as up-regulated expression of CD80, CD83, CD86, both MHC class I and II molecules, and CD205, with a simultaneous decrease in the expression of CD206 and the endocytic capacity. Interestingly, AME was not able to induce the production of TNF-alpha, IL-12p40, or IL-10, whereas lipopolysaccharides induced a substantial increase of all of the cytokines. CONCLUSION: Armillariella mellea induces maturation of human DCs through a unique mechanism without inducing cytokine expression.

An ethanol extract of Piper betle Linn. mediates its anti-inflammatory activity via down-regulation of nitric oxide.

The leaves of Piper betle (locally known as Paan) have long been in use in the Indian indigenous system of medicine for the relief of pain; however, the underlying molecular mechanisms of this effect have not been elucidated. The anti-inflammatory and immunomodulatory effects of an ethanolic extract of the leaves of P. betle (100 mg kg(-1); PB) were demonstrated in a complete Freund's adjuvant-induced model of arthritis in rats with dexamethasone (0.1 mg kg(-1)) as the positive control. At non-toxic concentrations of PB (5-25 microg mL(-1)), a dose-dependent decrease in extracellular production of nitric oxide in murine peritoneal macrophages was measured by the Griess assay and corroborated by flow cytometry using the nitric oxide specific probe, 4,5-diaminofluorescein-2 diacetate. This decreased generation of reactive nitrogen species was mediated by PB progressively down-regulating transcription of inducible nitric oxide synthase in macrophages, and concomitantly causing a dose-dependent decrease in the expression of interleukin-12 p40, indicating the ability of PB to down-regulate T-helper 1 pro-inflammatory responses. Taken together, the anti-inflammatory and anti-arthrotic activity of PB is attributable to its ability to down-regulate the generation of reactive nitrogen species, thus meriting further pharmacological investigation.